Fu Hongmei, Liu Changzhen, Flutter Barry, Tao Hua, Gao Bin
Rheumatology Unit, UCL Institute of Child Health, University College London, London, UK.
Mol Immunol. 2009 Oct;46(16):3198-206. doi: 10.1016/j.molimm.2009.08.012. Epub 2009 Sep 11.
Calreticulin (CRT) plays a critical role in MHC class I antigen processing and elicits peptide-specific CD8(+) T cell responses against tumours when administered with peptides. However, how CRT contributes to class I antigen processing and the mechanism of its adjuvant effect in anti-tumour responses, remain to be elucidated. Here we show that reduced class I expression in CRT deficient cells can be restored by the direct delivery of peptides into the ER or by incubation at low temperature. CRT deficient cells exhibited a TAP-deficient phenotype in terms of class I assembly, without loss of TAP expression or functionality. Furthermore, a higher concentration of antigen in the cytosol is required for specific T cell stimulation, suggesting that CRT has a functional role in the maintenance of the low peptide concentration threshold required in the ER for efficient antigen presentation. In the absence of CRT, ERp57 is up-regulated, which indicates that they collaborate with each other in class I antigen processing.
钙网蛋白（CRT）在MHC I类抗原加工过程中起关键作用，与肽一起给药时可引发针对肿瘤的肽特异性CD8(+) T细胞反应。然而，CRT如何促进I类抗原加工及其在抗肿瘤反应中的佐剂作用机制仍有待阐明。在这里，我们表明，通过将肽直接递送至内质网或在低温下孵育，可以恢复CRT缺陷细胞中降低的I类表达。CRT缺陷细胞在I类组装方面表现出TAP缺陷表型，而TAP表达或功能没有丧失。此外，特异性T细胞刺激需要胞质溶胶中更高浓度的抗原，这表明CRT在维持内质网中有效抗原呈递所需的低肽浓度阈值方面具有功能性作用。在没有CRT的情况下，ERp57上调，这表明它们在I类抗原加工中相互协作。
